Adenoid Cystic CarcinomaPhase 2NCT03999684
A Trial of All-trans Retinoic Acid (ATRA) in Advanced Adenoid Cystic Carcinoma
A Phase 2 study testing Tretinoin in people with Adenoid Cystic Carcinoma, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
This research is studying how safe and effective all-trans retinoic acid (ATRA), is to treat advanced adenoid cystic carcinoma (ACC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenoid Cystic Carcinoma
- What is being tested?
- Tretinoin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 Aug 2019to 15 Apr 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have histologically confirmed adenoid cystic carcinoma with evidence of recurrent, metastatic or advanced, unresectable disease that is not amenable to curative surgery with or without radiotherapy.
- Participants must have at least one RECIST v1.1 measurable non-CNS based lesion, as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) equal to or greater than 1 cm with CT scans or MR imaging.
- Participants must be willing to undergo fresh tissue core needle biopsy prior to study registration and repeat tumor biopsy while on study for correlatives. Willingness to provide blood samples for research throughout the study is also required.
- Prior systemic therapy: At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (4 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE Version 5.0 grade ≤ 1 (or tolerable grade 2) or back to baseline (except for alopecia or neuropathy). Any number of prior therapies for recurrent/metastatic ACC are permitted.
- Be ≥ 18 years of age on day of signing informed consent.
- Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A).
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- Participants must have documentation of a new or progressive lesion on a radiologic imaging study performed within 12 months prior to study registration (progression of disease over any interval is allowed) and/or new or worsening disease-related symptoms within 12 months prior to study registration. This assessment is performed by the treating investigator. Evidence of progression by RECIST v1.1 criteria is not required.
- Participants must have normal organ and marrow function as defined below (within 14 days prior to study registration):
- leukocytes ≥ 3,000/mcL
- absolute neutrophil count ≥ 1,500/mcL
- hemoglobin ≥ 9 g/dL without transfusion within 7 days of treatment
- platelets ≥ 100,000/mcL
- total bilirubin ≤ 2x upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤ 2.5x institutional ULN or ≤ 5x ULN for those with liver metastases
- serum creatinine ≤ 1.5x ULN OR
- creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above 1.5x ULN
- coagulation profile INR ≤ 1.5x ULN unless the participant is receiving an anticoagulant
- triglyceride level < 500 mg/dL or < 5.7 mmol/L
- cholesterol level < 400 mg/dL or < 10.34 mmol/L
- Baseline tumor measurements must be documented from imaging within 28 days prior to study registration. Other non-laboratory tests must be performed within 28 days prior to study registration.
- Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 14 days of study registration. Female subjects of childbearing potential should have a negative urine or serum pregnancy test repeated within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female and male subjects of childbearing potential must agree to use an adequate method of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of tretinoin administration. Contraception is required before starting the first dose of study medication through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. There is a significant risk of fetal malformation if pregnancy occurs while on tretinoin at any dose level, even if for short exposure periods.
- Be willing and able to provide written informed consent for the trial.
Who cannot join
- Metastatic disease impinging on the spinal cord or threatening spinal cord compression. Patients that have had previous treatment of disease with impinging on the cord with either surgery or radiotherapy with clinical or radiographic evidence of response or stability are eligible.
- Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment), and have no evidence of new or enlarging brain metastases. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability, because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Concurrent administration of other cancer specific therapy or investigational agents during the course of this study is not allowed.
- Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Subjects who are pregnant, or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because tretinoin has the potential for teratogenic or abortifacient effects. Breastfeeding should be discontinued if the mother is treated on this protocol. Women who could potentially become pregnant while undergoing treatment on this protocol must be willing to use 2 methods of contraception.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase II Trial of All-trans Retinoic Acid (ATRA) in Advanced Adenoid Cystic Carcinoma
This research is studying how safe and effective all-trans retinoic acid (ATRA), is to treat advanced adenoid cystic carcinoma (ACC).
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved all-trans retinoic acid (ATRA) for this specific disease but it has been approved for other uses.
The main purpose of this study is to see how effective all-trans retinoic acid (ATRA) is in treating tumor. Other reasons for conducting the study are:
- To determine for how long all-trans retinoic acid (ATRA) may reduce the size or slow down the growth of tumor
- To evaluate levels of circulating tumor DNA (ctDNA) released in the bloodstream as an indication of the disease activity
- To better understand mechanisms of tumor resistance to ATRA
- Conditions
- Adenoid Cystic Carcinoma
- Being tested
- Tretinoin
- Keywords
- Adenoid Cystic Carcinoma
- Medical subject headings
- Carcinoma, Adenoid Cystic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TretinoinDrug
Also called Tretin-X, ATRA
ATRA control normal cell growth, cell differentiation (the normal process of making cell different from each other), and cell death during embryonic development and in certain tissues later in life. Retinoids effects on the cells are controlled by receptors on the nucleus of each cell (nuclear receptors)
| Study group | Role | What they receive |
|---|---|---|
| Tretinoin | Experimental | -Participants will receive Tretinoin orally divided over two daily doses for days 1 through 14 of a 28-day cycle Receives: Drug: Tretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rate
CR 0, PR 0, SD 11, PD 5, UE 2
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. SD=stable disease, PD=progression of disease, UE=unevaluable
Measured: up to 8 months
Secondary outcomes (4)
Complete Response
CR rate captured up to 8 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. SD=stable disease, PD=progression of disease, UE=unevaluable
Measured: up to 8 months
Partial Response
PR rate captured up to 8 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. SD=stable disease, PD=progression of disease, UE=unevaluable
Measured: up to 8 months
Progression Free Survival
Median PFS or progression free survival
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. SD=stable disease, PD=progression of disease (Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions), UE=unevaluable
Measured: up to 8 months
Duration Of Therapeutic Response
Duration of CR+PR
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. SD=stable disease, PD=progression of disease, UE=unevaluable
Measured: up to 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2019
- Study start5 Aug 2019
- Primary completion15 Apr 2020
- Study completion15 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenoid Cystic CarcinomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- The V Foundation, Adenoid Cystic Carcinoma Research Foundation
- Responsible party
- Principal investigator, Glenn J. Hanna, Dana-Farber Cancer Institute
- Investigators
- Glenn J. Hanna, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03999684
- Sponsor's protocol ID
- 19-224
- Status last verified
- Jan 2023
- First submitted
- 25 Jun 2019
- Last updated
- 23 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of All-trans Retinoic Acid (ATRA) in Advanced Adenoid Cystic Carcinoma
- ClinicalTrials.gov ID
- NCT03999684
- Acronym / sponsor ID
- 19-224
- Conditions
- Adenoid Cystic Carcinoma
- Keywords
- Adenoid Cystic Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- The V Foundation, Adenoid Cystic Carcinoma Research Foundation
- Study start
- 5 Aug 2019 (actual)
- Primary completion
- 15 Apr 2020 (actual)
- Study completion
- 15 Apr 2020 (actual)
- First posted
- 27 Jun 2019 (actual)
- Results
- Posted 6 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research is studying how safe and effective all-trans retinoic acid (ATRA), is to treat advanced adenoid cystic carcinoma (ACC).
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved all-trans retinoic acid (ATRA) for this specific disease but it has been approved for other uses.
The main purpose of this study is to see how effective all-trans retinoic acid (ATRA) is in treating tumor. Other reasons for conducting the study are:
- To determine for how long all-trans retinoic acid (ATRA) may reduce the size or slow down the growth of tumor
- To evaluate levels of circulating tumor DNA (ctDNA) released in the bloodstream as an indication of the disease activity
- To better understand mechanisms of tumor resistance to ATRA
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tretinoin | Experimental | Drug: Tretinoin-Participants will receive Tretinoin orally divided over two daily doses for days 1 through 14 of a 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Participants must have histologically confirmed adenoid cystic carcinoma with evidence of recurrent, metastatic or advanced, unresectable disease that is not amenable to curative surgery with or without radiotherapy.
- Participants must have at least one RECIST v1.1 measurable non-CNS based lesion, as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) equal to or greater than 1 cm with CT scans or MR imaging.
- Participants must be willing to undergo fresh tissue core needle biopsy prior to study registration and repeat tumor biopsy while on study for correlatives. Willingness to provide blood samples for research throughout the study is also required.
- Prior systemic therapy: At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (4 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE Version 5.0 grade ≤ 1 (or tolerable grade 2) or back to baseline (except for alopecia or neuropathy). Any number of prior therapies for recurrent/metastatic ACC are permitted.
- Be ≥ 18 years of age on day of signing informed consent.
Key exclusion criteria (7 listed)
- Metastatic disease impinging on the spinal cord or threatening spinal cord compression. Patients that have had previous treatment of disease with impinging on the cord with either surgery or radiotherapy with clinical or radiographic evidence of response or stability are eligible.
- Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment), and have no evidence of new or enlarging brain metastases. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability, because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Concurrent administration of other cancer specific therapy or investigational agents during the course of this study is not allowed.
- Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TretinoinAlso: Tretin-X, ATRAATRA control normal cell growth, cell differentiation (the normal process of making cell different from each other), and cell death during embryonic development and in certain tissues later in life. Retinoids effects on the cells are controlled by receptors on the nucleus of each cell (nuclear receptors) | Drug | Tretinoin |
Primary outcome
Best Overall Response Rate
Time frame: up to 8 months
CR 0, PR 0, SD 11, PD 5, UE 2 Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. SD=stable disease, PD=progression of disease, UE=unevaluable
4 secondary outcomes
Complete Response
Time frame: up to 8 months
Partial Response
Time frame: up to 8 months
Progression Free Survival
Time frame: up to 8 months
Duration Of Therapeutic Response
Time frame: up to 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Glenn J. Hanna, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tretinoin in people with Adenoid Cystic Carcinoma, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response Rate (time frame: up to 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2023.